Evidence map›Paper›PMID 34215748›Full record

ArticleNature communications2021

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Yun-Fan Sun, Liang Wu, Shi-Ping Liu, Miao-Miao Jiang, Bo Hu, Kai-Qian Zhou, Wei Guo, Yang Xu, Yu Zhong, Xiao-Rui Zhou and 23 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 1 pooled it
13.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.

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  7. Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 9 institutions in 5 countries.

Yun-Fan Sun *Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.ORCID 0000-0001-9790-2761
Liang Wu *BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0001-6259-261X
Shi-Ping Liu *BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0003-0019-619X
Miao-Miao Jiang *BGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Bo Hu *Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.ORCID 0000-0001-9213-1304
Kai-Qian ZhouDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Wei GuoDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Yang XuDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Yu ZhongBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0001-6902-2732
Xiao-Rui ZhouBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Ze-Fan ZhangDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Geng LiuBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Sheng LiuBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Ying-Hong ShiDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Yuan JiDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.ORCID 0000-0002-2631-9082
Min DuDepartment of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Nan-Nan LiBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Gui-Bo LiBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0002-6141-4931
Zhi-Kun ZhaoBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0001-5161-7818
Xiao-Yun HuangBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
Li-Qin XuBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.ORCID 0000-0003-3377-3707
Qi-Chao YuBGI-Shenzhen, Shenzhen, Beishan Industrial Zone, Shenzhen, China.
David H PengDunwill Med-Tech, Shanghai, China.
Shuang-Jian QiuDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Hui-Chuan SunDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.
Michael DeanLaboratory of Translational Genomics, Division of Cancer Epidemiology & Genetics, National Cancer Institute Gaithersburg, Rockville, MD, USA.ORCID 0000-0003-2234-0631
Xiang-Dong WangZhongshan Hospital Institute of Clinical Science, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai, China.
Wen-Yuan ChungDepartment of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK.ORCID 0000-0003-0970-0639
Ashley R DennisonDepartment of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK.
Jian ZhouDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.ORCID 0000-0002-2118-1117
Yong HouZhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, People's Republic of China. houyong@genomics.cn.ORCID 0000-0002-0420-0726
Jia FanDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China. fan.jia@zs-hospital.sh.cn.ORCID 0000-0001-5158-629X
Xin-Rong YangDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China. yang.xinrong@zs-hospital.sh.cn.ORCID 0000-0002-2716-9338
Ministry of Education of the People's Republic of China · CNShenzhen University · CNFudan University · CNSun Yat-sen University · CNUniversity Hospitals of Leicester NHS Trust · GBNational Cancer Institute · USShanghai Medical College of Fudan University · CNSoutheast University · CNUniversity of Chinese Academy of Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Indexed as

Genetic HeterogeneityImmune EvasionAgedAnimalsBiomarkers, TumorCarcinoma, HepatocellularCell CycleCell Line, TumorChemokine CCL5Gene Expression Regulation, NeoplasticHumansLiver NeoplasmsMaleMiceMice, Inbred C57BLMiddle AgedBiomarkers, TumorChemokine CCL5

Identifiers

PMID34215748
PMCPMC8253833
OpenAlexW3176314022

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.